The neuropeptide α-melanocyte stimulating hormone (α-MSH) is an endogenous peptide hormone which has been found to exert anti-inflammatory responses in many organ systems, including the skin. α-MSH is generated from proteolytic cleavage of the precursor hormone proopiomelanocortin (POMC), which is also the precursor for the peptide hormones adrenocorticotrophin (ACTH), β-MSH, and γ-MSH (1). These peptide hormones, called melanocortins, were originally described for their pigment-inducing capabilities, but have since been implicated in many other protective processes. POMC and its derivatives are primarily products of the pituitary gland and hypothalamus but have also been shown to be produced locally in the skin (2, 3). α-MSH is endogenous to humans and primarily binds to the melanocortin receptor MC-1R, which is expressed in endothelial cells, fibroblasts, keratinocytes, and melanocytes in the skin (4) as well as in other cells such as monocytes, lymphocytes, and neutrophils (1). MC-4R, which is reportedly expressed in dermal papilla cells, and MC-5R, which has been found to be expressed in sebocytes and skin mast cells, also bind α-MSH (5). It is thought that α-MSH exerts its anti-inflammatory actions primarily by binding to MC-Rs but also through additional effector pathways such as antagonism to IL-1β(1). α-MSH has been shown to exhibit an array of immunosuppressive activities in vitro (6,10).
Despite decades of research, few agents have been successfully developed for eczematous inflammatory disorders. Topical corticosteroids have been extensively developed and utilized clinically to treat a wide range of inflammatory skin disorders for several decades but have many potential side effects that are exacerbated with continual use (11). Recently, calcineurin inhibitors such as tacrolimus and pimecrolimus have been clinically available to use as alternative nonsteroidal topical treatment agents; however, these compounds also have potential harmful side effects, and the FDA has issued a black box warning based on evidence that they are potentially carcinogenic (12-14).
New treatments for eczematous inflammatory disorders and other inflammatory skin disorders are needed as alternatives to corticosteroids, tacrolimus, and pimecrolimus, each of which have problematic side effects.